The considerable loss of crop productivity each year due to plant disease or pathogen invasion during pre- or post-harvest storage conditions is one of the most severe challenges to achieving the goals of food security for the rising global population. Although chemical pesticides severally affect the food quality and health of consumers, a large population relies on them for plant disease management. But currently, endophytes have been considered one of the most suitable biocontrol agents due to better colonization and acclimatization potential. However, a very limited number of endophytes have been used commercially as biocontrol agents. Isolation of endophytes and their screening to represent potential characteristics as biocontrol agents are considered challenging by different procedures. Through a web search using the keywords “endophytes as biocontrol agents” or “biocontrol mechanism of endophytes,” we have succinctly summarised the isolation strategies and different in vitro and in vivo biocontrol screening methods of endophytic biocontrol agents in the present review. In this paper, biocontrol mechanisms of endophytes and their potential application in plant disease management have also been discussed. Furthermore, the registration and regulatory mechanism of the endophytic biocontrol agents are also covered.